BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective To investigate the potential mechanisms by which the natural herbal monomer scutellarin alleviates ischemic stroke(IS)using network pharmacology and in vivo experimental validation.Methods Potential targets of scutellarin were predicted using SwissTargetPrediction and PharmMapper,and standardized via UniProt.IS-related differentially expressed genes(DEGs)were obtained from the GSE22255 dataset in the GEO database,with screening criteria of|log10FC|≥1 and P＜0.05.Venny 2.1.0 analysis was used to identify overlapping targets.Protein-protein interaction(PPI)networks were constructed using STRING and visualized in cytoscape.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed.Molecular docking was conducted using AutoDock Vina 1.5.6 to assess the binding affinity between scutellarin and hub targets.Middle cerebral artery occlusion(MCAO)mouse model was established and divided into sham,MCAO,and MCAO+scutellarin groups.Real-time PCR was used to detect mRNA expression of hub genes and phosphatidylinositol 3-kinase(PI3K)/Akt pathway components in the ischemic cortex.Results A total of 325 scutellarin targets and 2168 IS-related DEGs were identified,with 29 overlapping targets.GO analysis yielded 51 biological processes,5 cellular components,and 8 molecular functions.KEGG enrichment highlighted PI3K/Akt and metabolic pathways.PPI analysis identified Caspase-3,epidermal growth factor receptor(EGFR),prostaglandin-endoperoxide synthase 2(PTGS2),peroxisome proliferator activated receptor alpha(PPARA),and interleukin-2(IL-2)as key hub proteins.Molecular docking showed strong binding affinities between scutellarin and these proteins.Real-time PCR result confirmed that scutellarin modulated the expression of hub genes and activated the PI3K/Akt pathway.Conclusion In the MCAO mouse model,scutellarin exerts neuroprotective effects by modulating targets such as CASP3,EGFR,PTGS2,PPARA,and IL-2,and activating the PI3K/Akt signaling pathway,exhibiting multi-target and multi-pathway characteristics.

BACKGROUND:In recent years,a number of studies have confirmed that gut microbiome regulates bone metabolism through multiple pathways,and this field has become a research hotspot in orthopedics and microbiology.However,there is still no literature metrology and visual analysis on this field.OBJECTIVE:To explore the research status,hot spots and development trends in the field of gut microbiome regulation of bone metabolism,and to provide certain data support and reference for subsequent studies.METHODS:The Web of Science core collection database was used as the retrieval platform to retrieve the related literature in the field of intestinal flora regulating bone metabolism from 2004 to 2024.Citespace software was used to visually analyze the included literature and generate a visual atlas.RESULTS AND CONCLUSION:(1)A total of 1,035 papers were included in this study.In the past 20 years,the number of publications in the field of gut microbiome regulation of bone metabolism has shown a significant growth trend,with the United States and China dominating research and publication activities in this field.Harvard University and the University of California system are the research institutions with the highest number of published papers and research centrality in this area,and Professor Pacifici R of Emory University is the most prolific author.(2)Inflammatory bowel disease,chain fatty acids,bone marrow are the core keywords in this field.Postmenopausal osteoporosis,rheumatoid arthritis,oxidative stress,mitochondrial dysfunction are the latest research frontiers in this field.(3)Among the top 10 cited papers,4 discussed the mechanism of short-chain fatty acids affecting bone metabolism;3 investigated the pathogenesis and therapeutic potential of intestinal flora in postmenopausal osteoporosis,glucocorticoid-induced osteoporosis,and senile osteoporosis;1 discussed the relationship between intestinal inflammation,intestinal flora,parathyroid hormone,and bone metabolism;and 1 examined the effects of Lactobacillus rhamnosus and T cells on the gut microbiome and bone metabolism.(4)NUTRIENTS has the most papers,while ENDOCRINOLOGY& METABOLISM has the most citations.(5)Based on literature co-citation analysis and keywords,further exploration is needed on the specific pathogenesis and treatment strategies of gut microbiome in postmenopausal osteoporosis and rheumatoid arthritis,revealing the molecular mechanism of regulating gut microbiota to inhibit oxidative stress and improve mitochondrial dysfunction affecting bone metabolism,and translating mechanism research into clinical application,which all constitute the future research directions and trends in this field.

BACKGROUND:At present,modern medical treatment has certain limitations on the treatment of knee osteoarthritis.Traditional Chinese medicine alkaloids can effectively prevent and treat knee osteoarthritis through various mechanisms. OBJECTIVE:To review the mechanism of alkaloids in traditional Chinese medicine in the prevention and treatment of knee osteoarthritis,providing a scientific basis for the clinical development of drugs for the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Web of Science and Google Scholar were retrieved for relevant literature published from database inception to May 2024.The key words were"knee osteoarthritis""osteoarthritis""osteoclast""chondrocyte""alkaloids"in Chinese and English.Duplicates and obsolete non-referenced literature were excluded,and a total of 68 eligible papers were included for further review. RESULTS AND CONCLUSION:Although traditional Chinese medicine has a long history of treating knee osteoarthritis,only a small number of natural compounds are in the preclinical stage of research against knee osteoarthritis.Alkaloids have a greater potential for the prevention and treatment of knee osteoarthritis,among which,sophocarpidine,oxymatrine,sinomenine,and betaine have been shown to be effective in the prevention and treatment of knee osteoarthritis by modulating multiple signaling pathways.Alkaloids can delay the progression of knee osteoarthritis by inhibiting inflammatory response,exerting antioxidant response,inhibiting chondrocyte apoptosis,promoting chondrocyte proliferation,and inhibiting osteoclast formation and differentiation.

BACKGROUND:In recent years,postmenopausal osteoporosis has been widely concerned by the society.With the gradual deepening of the research on animal models,animal models have become an important means of modern traditional Chinese medicine research as well as the experimental basis.Therefore,it is particularly important to understand the current status,hotspots,and development trend of the research on animal models.OBJECTIVE:To analyze the research status,hotspots,and development trend of animal models of postmenopausal osteoporosis at home and abroad,and to provide a certain theoretical foundation and reference basis for subsequent research.METHODS:Using"Subject=Postmenopausal osteoporosis AND Subject line=Mouse+Rabbit+Dog+Pig+Sheep+Monkey+Fish+Laboratory animals+Animal experimentation"in Chinese as the search formula,we searched for relevant literature published from January 1,1999 to October 1,2023 in CNKI and WanFang databases.Meanwhile,the articles published from January 1,1999 to October 1,2023 in the Web of Science Core Collection database were searched using"TS=(Postmenopausal osteoporosis)AND TS=(mouse OR mice OR rat OR rabbit OR dog OR swine OR pig OR sheep OR monkey OR fish OR flies OR"laboratory animal"OR"experiment animal"as the search formula.CiteSpace software was applied to visualize and analyze the authors,institutions,countries,keywords,and literature co-citations.RESULTS AND CONCLUSION:(1)After analyzing and screening,1 238 documents were included in the CNKI and WanFang databases,and 3 419 documents were included in the Web of Science Core Collection database.The overall number of articles issued since 1999 has been on an upward trend,with the highest research centrality in the United States,the highest number of articles issued in China.Moreover,the institution with the highest research centrality is the University of California.(2)After removing the keywords directly related to the article topics and synthesizing the co-occurrence frequency and centrality,"biomechanics,""Zuo Gui Wan,""alendronate,""breast cancer,"and"biochemical indicators"are in the core of the research field.(3)According to the analysis of co-citations,among the top 10 cited documents,5 of them are related to the treatment measures and clinical efficacy of postmenopausal osteoporosis.(4)Based on the analysis of keywords and co-cited literature,investigations on osteoblast formation and the mechanism of bone formation,the mechanism of metabolomics,the treatment of traditional Chinese medicine,signaling pathway,parathyroid hormone treatment,and sclerostin antibody treatment are the hot research topics now and the future research trends.

BACKGROUND:In recent years,with the deepening of macrophage research,researchers have found that the pro-inflammatory and anti-inflammatory functions of macrophage polarization play a crucial role in the occurrence and progression of osteoarticular diseases.OBJECTIVE:To analyze the current status,hotspots,and development trends of macrophage polarization in osteoarticular diseases in order to provide reference for the subsequent scientific research work.METHODS:Using TS=("polarization of macrophages or macrophage polarization or macrophages polarization")AND TS=("arthritis or osteoarthritis or osteoporosis or degeneration intervertebral disc or necrosis of femoral head or rheumatoid arthritis")as the search formula,relevant literature addressing macrophage polarization in osteoarticular diseases were collected from the Web of Science Core Collection SCI-Expanded from January 01,2014 to June 01,2024.Citespace 6.3.R1 software was used for visual analysis of the publishing countries/regions,institutions,authors,journals,citation reference,and keywords,and then knowledge maps were drawn.RESULTS AND CONCLUSION:(1)A total of 420 papers were included after analysis and retrieval.The overall trend of publication volume is rising.The country with the highest volume and degree centrality is China.The institution with the most publications is Shanghai Jiao Tong University.The author with the most publications is Cai Daozhang.The journal with the most publications is International Immunopharmocology.(2)By integrating the frequency and centrality of keywords and excluding keywords directly related to the topic,it is known that the core keywords in this field are apoptosis,cartilage,differentiation,gene expression,and cytokines.(3)In the co-citation analysis of papers,among the top 10 cited documents,7 papers discuss the pathogenesis or therapeutic potential of macrophages in diseases,2 papers focus on the development of drugs or materials targeting macrophage polarization,and 1 paper reviews the current status of arthritis research.(4)Combining the co-citation analysis of papers and keywords,the current research hotspots focus on synergistic effect,the occurrence and regulatory mechanisms of polarization,the mechanism of transcriptomics,and the impact on related diseases and targeted tissues.As well,developing biomaterials with the function of regulating macrophage polarization and regulating the phenotype of macrophage polarization through drug targeting delivery systems may become the future research trends.

Objective To propose an improved Bouc-Wen model to alleviate the nonlinear effect of the hysteresis displacement of piezoceramics and enhance the motion control accuracy of the nano-displacement platform.Methods Firstly,two fine-tuning parameters including the asymmetric term and the input bias term were added to the classical Bouc-Wen model to eliminate the deviation of the starting and ending positions of the hysteresis curve,so as to obtain an improved Bouc-Wen model simulating the hysteresis displacement characteristics of piezoceramics on the nano-displacement platform.Secondly,the parameters of the improved Bouc-Wen model were identified based on the particle swarm optimization algorithm,and an inverse feedforward structure was adopted to realize the linearized control of the output displacement.Finally,an experimental system was built to verify the linearized control effect of the improved Bouc-Wen model.Results The hysteresis curve of the improved Bouc-Wen model fitted the actual voltage-displacement curve of piezoceramics significantly better when compared with that of the traditional model,which had a 56%reduction in the fitting error and a 0.03 μm error between the desired and actual displacements during the linearized output control with a driving voltage of 0-60 V and a maximum travel of about 4 μm.Conclusion The improved Bouc-Wen model behaves well in hysteresis displacement fitting and linearized output control,and a new idea is provided for enhancing the motion control accuracy of the nano-displacement platform.[Chinese Medical Equipment Journal,2025,46(8):25-31]

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.